We have previously shown that cocaine is toxic to fetal nigral dopamine neurons from E15 rat fetuses using in vitro cell culture. Fetal nigral cells incubated in culture with varying doses of cocaine showed significant reductions in cell survival between 3 × 10-10M and 3× [Illegible Text] M of cocaine. To determine whether peak cocaine values in fetal amniotic fluid and brain approximated the neurotoxic dosages observed using in vitro cell culture, we evaluated the response to a single subcutaneous (s.c.) injection of 30 mg/kg cocaine HCl in anesthetized pregnant rats (n=5) on day 15 of gestation. Fetal amniotic fluid and brain were harvested from a different fetus every 10 min (from 0-90 min) in order to examine the timing and concentration of cocaine and its metabolites. Amniotic fluid and brain samples were extracted using standard techniques and concentrated to allow for maximum sensitivity for GC-MS cocaine detection. Cocaine was evident in both amniotic fluid and fetal brain as early as 10 min post-injection. Cocaine levels peaked in amniotic fluid at 50 min(595±367 ng/ml) and in fetal brain at 60 min (548±188 ng/g protein). Cocaine metabolites benzoylecgonine (BE) and ecgonine methylester(EME) were detectable in the fetuses of only 1 dam. In the fetuses of this dam, BE peaked at 60 min (249 ng/ml) and tapered to 5 ng/ml by 90 min, but was absent in brain. EME was sporadically evident at the limits of detection in brain. This relatively moderate dose of cocaine (30 mg/kg) produced fetal brain cocaine levels (1.61 × 10-9M) that were sufficient to induce significant reductions in fetal nigral cell survival in culture(Buhrfiend et al., 1995). Cocaine abuse in clinical populations where the main route of administration is the inhalation of crack would likely produce significantly higher fetal brain concentrations than those reported here, thus increasing the likelihood of neurotoxicity in the developing fetus.Figure

figure 1

Figure 1